Vudalimab for Advanced Gynecologic and Genitourinary Cancers

Recruiting at 18 trial locations

Overseen By Jolene Shorr

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xencor, Inc.

Must be taking: LHRH analogues

Must not be taking: CTLA4 agents, PD1 therapies

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

170 Participants Needed

Trial Summary

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other anticancer therapies, except for certain hormone therapies for prostate cancer. If you're on systemic corticosteroids or immunosuppressive medications, you must stop them 14 days before starting the trial drug.

What data supports the idea that Vudalimab for Advanced Gynecologic and Genitourinary Cancers is an effective treatment?

The available research shows that Vudalimab, a bispecific antibody targeting PD-1 and CTLA-4, has the potential to be effective in treating advanced cancers. It works by activating certain immune cells, which can help the body fight cancer. Although clinical trials are still in the early stages, the research suggests that Vudalimab might perform better than the combination of other treatments like nivolumab and ipilimumab, which are used for similar purposes. However, more data is needed to confirm its effectiveness specifically for advanced gynecologic and genitourinary cancers. ^{1 2 3 4 5}

What safety data is available for Vudalimab (XmAb20717)?

The safety data for Vudalimab (XmAb20717) is not directly mentioned in the provided research abstracts. However, the development of bispecific antibodies targeting PD-1 and CTLA-4, like Vudalimab, aims to enhance therapeutic efficacy while potentially minimizing toxicity. The research on similar checkpoint inhibitors, such as ipilimumab (CTLA-4) and pembrolizumab (PD-1), indicates that these treatments are associated with immune-related adverse events. Combination approaches involving CTLA-4 and PD-1/PD-L1 blockade are being investigated to improve efficacy and manage toxicity. The development of bispecific antibodies, such as MEDI5752, is focused on optimizing therapeutic response and minimizing toxicity, which may provide insights into the safety profile of Vudalimab. ^{2 6 7 8 9}

Is the drug Vudalimab promising for treating advanced gynecologic and genitourinary cancers?

Yes, Vudalimab is promising because it targets two important molecules, PD-1 and CTLA-4, which help the immune system fight cancer. This dual action could potentially be more effective than using separate drugs for each target. Early research shows encouraging results in similar cancers, making it an exciting area for further study. ^{1 4 6 10 11}

What is the purpose of this trial?

This trial is testing a new drug called vudalimab in patients with hard-to-treat advanced gynecologic and genitourinary cancers. The drug aims to boost the immune system's ability to fight cancer by making cancer cells more visible to immune cells.

Research Team

Jolene Shorr

Principal Investigator

Xencor, Inc.

Eligibility Criteria

This trial is for adults with certain advanced gynecologic and genitourinary cancers that have worsened despite all approved treatments or when no suitable treatments are available. Participants must be in good physical condition, agree to use effective birth control, and commit to the study schedule. Those who've had more than two chemo treatments for some cancers or recent other cancer therapies can't join.

Inclusion Criteria

Able to provide written informed consent

My cancer type has been confirmed through lab tests.

I am willing and able to follow the study's schedule completely.

Exclusion Criteria

Subject is pregnant or breastfeeding or planning to become pregnant while enrolled in the study

I have previously been treated with specific immunotherapy.

I do not have HIV, hepatitis C, or hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive vudalimab in tumor-specific cohorts to evaluate efficacy and safety

12 weeks

Stage 2 Treatment

Additional subjects are enrolled in cohorts with ORR ≥ 20% for further evaluation

Variable, based on cohort expansion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vudalimab (XmAb20717)

Trial Overview The trial is testing Vudalimab (XmAb20717) on patients with specific advanced cancers of the reproductive organs and urinary system. It's an open-label Phase 2 study, meaning both researchers and participants know what treatment is being given, aiming to assess how well it works and its safety.

Participant Groups

Group I: vudalimab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Findings from Research

The bispecific antibody described in patent US2019161548 targets both PD-1 and CTLA-4, which are important immune checkpoints in cancer, and has been shown to enhance the activation and proliferation of CD8+ T cells and stimulate CD4+ T cells.

Clinical trials are currently underway to assess the safety and effectiveness of this bispecific antibody, with hopes that it may outperform the existing combination therapy of nivolumab and ipilimumab in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. Perez-Santos, M.[2021]

In a study of 204 patients with advanced urothelial carcinoma, those receiving maintenance avelumab therapy showed longer overall survival compared to those receiving second-line pembrolizumab or cytotoxic chemotherapy, although progression-free survival was not significantly different.

Patients who started maintenance avelumab therapy within 6 weeks of completing first-line chemotherapy had a higher disease control rate (77%) compared to those who waited longer, suggesting that early initiation of avelumab may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Miyake, M., Shimizu, T., Oda, Y., et al.[2023]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

Zimberelimab (GLS-010) is a highly effective human monoclonal antibody that binds strongly to the PD-1 receptor, blocking its interaction with PD-L1/2, which is crucial for T cell activation.

In preclinical studies, GLS-010 demonstrated significant anti-tumor effects in mice, indicating its potential as a promising treatment for cancer, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Lou, B., Wei, H., Yang, F., et al.[2022]

In a preoperative trial involving 12 patients with localized bladder cancer, the anti-CTLA-4 antibody ipilimumab demonstrated a tolerable safety profile, with most adverse events being mild (grade 1/2).

The treatment led to measurable immune responses, specifically an increase in CD4+ICOShi T cells, which correlated with improved overall survival in a retrospective analysis of metastatic melanoma patients, suggesting that these T cells could serve as a marker for clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Carthon, BC., Wolchok, JD., Yuan, J., et al.[2023]

Checkpoint-blocking antibodies, like ipilimumab, enhance the immune system's ability to recognize and eliminate tumors by blocking the CTLA-4 receptor, which normally inhibits T-cell activation.

The review discusses the clinical development of CTLA-4 blocking antibodies, highlighting their effectiveness in cancer treatment, associated toxicities, and the exploration of biomarkers to predict patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists. Callahan, MK., Wolchok, JD.[2017]

Immunologic checkpoint blockade using antibodies like ipilimumab (CTLA-4) and pembrolizumab (PD-1) has shown effectiveness in treating advanced melanoma and is expected to gain further approvals for other cancers.

These treatments can lead to unique immune-related adverse events and unusual tumor response patterns, prompting research into combination therapies to potentially enhance their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Blockade in Cancer Therapy. Postow, MA., Callahan, MK., Wolchok, JD.[2022]

Avelumab demonstrated antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma, achieving a complete or partial response in 17% of treated patients, including 6% with complete responses.

The safety profile of avelumab was manageable, with most treatment-related adverse events being mild (grade 1-2), although there were serious adverse events in 8% of patients, including one treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Patel, MR., Ellerton, J., Infante, JR., et al.[2022]

The combination of anti-PD-1 and anti-CTLA4 antibodies has improved cancer treatment outcomes but is often limited by serious immune-related side effects and resistance.

MEDI5752, a new bispecific antibody targeting both PD-1 and CTLA4, aims to enhance treatment effectiveness by focusing on T cells that have already encountered antigens, potentially increasing efficacy while reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity. Burton, EM., Tawbi, HA.[2021]

Recent advancements in treating genitourinary tumors, particularly renal cell and prostate cancer, involve using immune checkpoint inhibitors like ipilimumab and nivolumab to enhance the immune response against cancer cells.

Initial data shows promising results for these immunomodulating antibodies, highlighting the need for further investigation in large controlled trials to fully understand their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic checkpoints blockade in renal cell, prostate, and urothelial malignancies. Bracarda, S., Altavilla, A., Hamzaj, A., et al.[2015]

The JAVELIN Ovarian 200 trial is the first Phase III study to investigate the effectiveness of avelumab, a PD-L1 checkpoint inhibitor, in treating women with platinum-resistant ovarian cancer, involving multiple treatment arms to assess its efficacy.

The trial will measure overall survival and progression-free survival as primary outcomes, providing valuable insights into the potential benefits of avelumab alone or in combination with doxorubicin compared to doxorubicin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. Pujade-Lauraine, E., Fujiwara, K., Dychter, SS., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Blockade in Cancer Therapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Immunologic checkpoints blockade in renal cell, prostate, and urothelial malignancies. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. [2022]